CMV is a major cause of inflammatory organ disease in immunosuppressed patients. To elucidate the mechanisms of CMV-induced inflammation, tumor necrosis factor alpha (TNF alpha) was studied in AIDS patients with CMV colitis. In Situ hybridization techniques were used on colonic mucosa from AIDS patients and normal controls. Positive hybridization of TNF alpha probe to mRNA was obtained with colonic mucosa from patients, and was associated with CMV but not HIV-1 infected cells. Also, a patient- derived isolate of CMV induced primary human blood monocytes to express TNF-alpha mRNA and increased the levels of secreted TNF-alpha. Thus, CMV induction of TNF-alpha may play a central role in CMV-induced inflammation. Furthermore, because of the known effects of TNF-alpha on the expression of HIV-1 provirus, CMV may be a co-factor in activation of latent HIV-1, without a requirement for co-infection of cells by the two viruses.